Abstract
MYC over-expression as determined by molecular means has been reported as a favorable prognostic biomarker in colorectal carcinoma (CRC). However MYC expression analysis is not available in the routine clinical setting. We investigated whether immunohistochemistry (IHC) for the myc protein using a novel commercially available rabbit monoclonal antibody [clone Y69] which is currently in widespread clinical use for lymphoma diagnosis could be used to predict outcome in resected CRC. Myc IHC was performed on a tissue microarray (TMA) comprising a retrospective cohort of 1421 CRC patients and scored blinded as to all clinical and pathological data. IHC was also performed on a subcohort of whole section CRCs to assess staining characteristics and concordance with TMA expression. MYC over-expression was found in 980 (69%) of CRCs and was associated with tumor stage and DNA mismatch repair/BRAF status. There was substantial agreement between TMA and whole section myc IHC (kappa = 0.742, p<0.01). CRCs with MYC over-expression demonstrated improved 5-year survival (93.2% vs. 57.3%), with the effect significantly modulated by the dominant effect of tumor stage, age at diagnosis and lymphovascular space invasion status on survival. We conclude that myc status as determined by IHC alone can be used to predict overall survival in patients with CRC undergoing surgical resection.
Highlights
Dysregulation of MYC (HGNC:7553) is an early consequence of activating mutations in APC(HGNC:583), a key driver mutation in the adenoma-carcinoma pathway in colorectal cancer (CRC)
The role of MYC over-expression in driving CRC tumorigenesis has been confirmed by gene expression profiling studies [3], and more recently by CRC genome-wide analysis as part of the Cancer Genome Atlas Network initiative [4]
A novel highly sensitive and specific rabbit monoclonal antibody directed against the myc protein has become available
Summary
Dysregulation of MYC (HGNC:7553) is an early consequence of activating mutations in APC(HGNC:583), a key driver mutation in the adenoma-carcinoma pathway in colorectal cancer (CRC). Testing for MYC over-expression in CRC is not currently available, feasible or warranted in the routine clinical setting. A novel highly sensitive and specific rabbit monoclonal antibody directed against the myc protein (clone Y69) has become available. This antibody has been validated in the routine clinical setting in formalin fixed paraffin embedded tissue, where myc immunohistochemsitry in combination with bcl immunohistochemistry, has been used to identify the poor prognostic subgroup of non-Hodgkin lymphoma known as ‘double hit lymphoma’. [6,7] MYC and BCL2 expression as determined by immunohistochemsitry in formalin fixed paraffin embedded tissue has rapidly become part of the routine diagnostic assessment of patients with high grade B-cell lymphoma. This antibody has been validated in the routine clinical setting in formalin fixed paraffin embedded tissue, where myc immunohistochemsitry in combination with bcl immunohistochemistry, has been used to identify the poor prognostic subgroup of non-Hodgkin lymphoma known as ‘double hit lymphoma’. [6,7] MYC and BCL2 expression as determined by immunohistochemsitry in formalin fixed paraffin embedded tissue has rapidly become part of the routine diagnostic assessment of patients with high grade B-cell lymphoma. [8]
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